A critical issue in the design and development of radiopharmaceuticals that contain a radiometal is the formation of kinetically inert complexes of the radiometal. Kinetic inertness and high in vivo stability are essential requirements for radiolabeled chelates that will be conjugated to specific targeting vectors (receptor avid peptides) through a linker arm. These radiometal chelate properties will (1) ensure delivery of the radiometal to the tumor site with the specific targeting vector; (2) minimize non-specific binding (i.e., high kinetic inertness will minimize loss of the radiometal from the chelate); and (3) minimize the radiation dose to normal tissues. Although several examples of BFCA design and new complexation strategies using Tc(V) and Tc(I) species are known to date, examples that demonstrate direct utility of generator produced 99m TcO4 - (or 188 REO4 - ) in stabilizing Tc(VlI)-BFCA cores for labeling peptides are still rare. Development of peptide labeling protocols that involve Tc(VlI), via 99m TcO4 - , stabilized by specific BFCAs, without the intervention of reducing agents/chemical cocktails, would provide a major boost in our abilities to label tumor specific and receptor avid peptides in general and particularly those peptides that contain reduction/chemically susceptible groups within the backbone. Development of functional and adaptable chelating agents and optimization of bioconjugation strategies, toward functionalization of BFCAs (or the radiolabeled BFCs), with biomolecules that express high affinity to antigens on carcinomas and metastases, would have a major impact on the rate and quality of highly sophisticated in vivo disease targeting radiopharmaceuticals. Our approach to these important issues is to design and evaluate kinetically inert technetium (VII) (and rhenium (VII)) complexes stabilized via functionalized phosphinimine cores (i.e., R1R2R3P=NTcO3 or R1R2R3P=NReO3), which will be conjugated to receptor avid peptides. The specific aims for this developmental application are: 1. Design, synthesis and characterize a series of Tc(VlI) (and Re(VII)) complexes of the general formula R1R2R3P=NMOn-x (M = TC or Re; n = 3, x = 0; n =2, x= 0; R1, R2 and R3 represent functionalized phosphinimine P=N backbone with imine, thioether or carboxylate functionalities). 2. Evaluate the in vitro and in vivo properties (i.e., serum stability, favorable clearance from non- target tissues, lipophilicity) of the 99m Tc labeled phosphinimine compounds to determine the lead compounds for further development. 3. Conjugate the lead chelates to heat stable STh and octreotide peptide analogs to demonstrate the feasibility of utilizing the phosphinimine based Tc(VII) BFCA synthons for radiolabeling peptides that contain disulfide bonds. 4. Evaluate the in vitro receptor binding affinity of these phosphinimine Tc(VII) -peptide conjugates for human colon cancer and somatostatin receptor positive cancer cells, respectively. 5. Investigate the in vivo pharmacokinetic characteristics of the lead STh and octreotide phosphinimine Tc(VII) conjugates.